Anxiety and tension of differing cause and intensity cannot be satisfactorily treated even today in all cases. Since approximately 1960, benzodiazepine derivatives have been employed as a matter of priority for the treatment of anxiety and tension. Substances having such a profile in general have a calming and emotion-damping action. These medicaments are a great help in the short term, but even in therapeutic doses side effects such as sedation, drowsiness and decreased responsiveness occur.
There can be a negative effect on mental processes due to sedation. Partly, ataxia and coordination disorders are to be observed, which affect the functional capacity. On continuous use, these benzodiazopine compounds lead to habituation effects, so-called tolerance. The efficacy of the preparation becomes lower and the dose has to be increased. A psychological dependence, moreover even a physiological dependence, can develop. Complicated withdrawal phenomena therefore occur in withdrawal trials.
The most important representatives of the anxiolytics on the market are the active compounds diazepam, clonazepam and medazepam. Plasma concentrations of 300 to 400 ng/ml are necessary to achieve an anxiolytic action of diazepam. The side effects mentioned, such as sedation and psychomotor disorders, which are manifested in daytime sedation, drowsiness and restricted attentiveness and responsiveness however, also occur, at the same concentrations. Severe "hangover" effects can occur, which are likewise associated with drowsiness, impairment of intellectual and motor capacities, and prolonged reaction time. The anxiolytic action of clonazepam is masked by sedating or hypnotic action. High doses of medazepam are also associated with hypnotic, muscle-relaxing phenomena.
All three anxiolytics potentiate the action of numerous centrally active pharmaceuticals and of alcohol. In this case, after administration of the individual substance seffects can occur which are barely noticeable.
Until now, there has been no success in achieving a satisfactory therapeutic standard in the case of relatively long-lasting anxiety states. A therapy-outlasting action of anxiolytic medicaments is presently also not adequately guaranteed.